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Öğe Autologous hematopoietic progenitor cell mobilization and collection in adult patients presenting with multiple myeloma and lymphoma: A position-statement from the Turkish Society of Apheresis (TSA)(Pergamon-Elsevier Science Ltd, 2017) Tekgunduz, Emre; Arat, Mutlu; Goker, Hakan; Ozdogu, Hakan; Kaynar, Leylagul; Cagirgan, Seckin; Erkurt, Mehmet Ali; Vural, Filiz; Kiki, Ilhami; Altuntas, Fevzi; Demirkan, FatihAutologous hematopoietic cell transplantation (AHCT) is a routinely used procedure in the treatment of adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and relapsed/refractory settings. Successful hematopoietic progenitor cell mobilization (HPCM) and collection are the rate limiting first steps for application of AHCT. In 2015, alinost 1700 AHCT procedures have been performed for MM, HL and NHL in Turkey. Although there are recently published consensus guidelines addressing critical issues regarding autologous HPCM, there is a tremendous heterogeneity in terms of mobilization strategies of transplant centers across the world. In order to pave the way to a more standardized HPCM approach in Turkey, Turkish Society of Apheresis (TSA) assembled a working group consisting of experts in the field. Here we report the position statement of TSA regarding autologous HPCM mobilization strategies in adult patients presenting with MM and lymphoma. (C) 2017 Elsevier Ltd. All rights reserved.Öğe Current practice of autologous hematopoietic progenitor cell mobilization in adult patients with multiple myeloma and lymphoma: The results of a survey from Turkish hematology research and education group (ThREG)(Pergamon-Elsevier Science Ltd, 2017) Tekgunduz, Emre; Demirkan, Fatih; Vural, Filiz; Goker, Hakan; Ozdogu, Hakan; Kiki, Ilhami; Aydogdu, Ismet; Kaynar, Leylagul; Erkurt, Mehmet Ali; Cagirgan, Seckin; Besisik, Sevgi; Dagdas, Simten; Koca, Ebru; Kadikoylu, Gurhan; Gunduz, Eren; Yilmaz, Mehmet; Bekoz, Hulseyin; Ural, Ali Ugur; Basturk, Abdulkadir; Arat, Mutlu; Albayrak, Murat; Ozturk, Erman; Akyol, Alev; Bolaman, Ali Zahit; Nevruz, Oral; Ozkan, Hasan Atilla; Ozgur, Gokhan; Altuntas, FevziAutologous hematopoietic cell transplantation (AHCT) is an established treatment option for adult patients presenting with multiple myeloma (MM), Hodgkin lymphoma (HL) and various subtypes of non-Hodgkin lymphoma (NHL) in upfront and/or relapsed/refractory disease settings. Although there are recently published consensus guidelines addressing critical issues regarding autologous hematopoietic progenitor cell mobilization (HPCM), mobilization strategies of transplant centers show high variability in terms of routine practice. In order to understand the current institutional policies regarding HPCM in Turkey and to obtain the required basic data for preparation of a national positional statement on this issue, Turkish Hematology Research and Education Group (ThREG) conducted a web-based HPCM survey. The survey was designed to include multiple-choice questions regarding institutional practice of HPCM in adults presenting MM, HL, and NHL. The representatives of 27 adult HCT centers participated to the study. Here we report the results of this survey shedding light on the real world experience in Turkey in terms of autologous HPCM mobilization strategies in patients presenting with MM and lymphoma. (C) 2017 Elsevier Ltd. All rights reserved.Öğe Early Access Program Results From Turkey and a Literature Review on Daratumumab Monotherapy Among Heavily Pretreated Patients With Relapsed/Refractory Myeloma(Cig Media Group, Lp, 2020) Beksac, Meral; Aydin, Yildiz; Goker, Hakan; Turgut, Mehmet; Besisik, Sevgi Kalayoglu; Cagirgan, Seckin; Tekgunduz, EmreThe present study investigated the efficacy and safety profile of daratumumab monotherapy in 42 patients with relapsed refractory multiple myeloma through a Turkish early access program. the current findings have confirmed the efficacy of daratumumab monotherapy in heavily pretreated patients with refractory multiple myeloma because of the deep and durable responses and favorable safety and tolerability profile. Background: in countries where frontline drug approval is limited to first-generation proteasome inhibitors or immunomodulatory drugs, relapses have been both more frequent and less durable. We investigated real world data on the efficacy and safety of daratumumab monotherapy among patients with relapsed refractory multiple myeloma (RRMM) from Turkey using a prospective early access program. Patients and Methods: A total of 42 patients with RRMM after a minimum of 3 previous lines of proteasome inhibitor/immunomodulatory drug-based treatments were included from 25 centers across Turkey. Daratumumab monotherapy was administered intravenously at a dose of 16 mg/kg weekly (cycles 1-2), on alternate weeks (cycles 3-6), and monthly thereafter. Results: the median daratumumab monotherapy duration was 5.5 months (range, 0.2-28.7 months). the overall response rate was 45.2%, including 14 (33.3%) partial responses, 4 (9.5%) very good partial responses, and 1 (2.4%) complete response. the median duration of response was 4.9 months. the median progression-free survival (PFS) was 5.5 (95% confidence interval, 2.6-8.4 months) with 12- and 18-month PFS rates of 35.7% and 31.0%, respectively. the median overall survival was not reached; the 12- and 18-month overall survival rates were 64.3% and 59.5%, respectively. the depth of response had a significant effect on PFS (log-rank test, P = .026). Overall, of the 76 adverse events reported, 33 (43.4%) were grade >= 3; only 4 (9.52%) were grade 3 infusion-related reactions. No infusion-related reactions or adverse events led to treatment discontinuation. Conclusion: the present findings from our daratumumab early access program have confirmed the efficacy and safety profile of daratumumab monotherapy in heavily pretreated Turkish patients with RRMM.Öğe Ibrutinib: From Molecule to Medicine(Akad Doktorlar Yayinevi, 2014) Ayyildiz, Orhan; Demirkan, Fatih; Goker, Hakan; Haznedaroglu, Ibrahim C.; Ilhan, Osman; Kaynar, Leyla G.; Ozdemir, Evren; Saydam, Güray; Sayinalp, Nilgun; Sahin, Fahri; Turgut, Mehmet; Unal, Ali; Vural, FilizBruton's tyrosine kinase (BTK) inhibitor Ibrutinib (PCI-32765) is a novel targeted-therapeutic agent modulating BCR, which serves as a covalent irreversible inhibitor of BTK. Ibrutinib significantly alters the composition of the tumor microenvironment in CLL, affecting soluble as well as cellular molecular elements without myelosupression. Ibrutinib is clinically developed as an orally administered anti-cancer agent with lead indications in relapse/refractory and in treatment-naive patients with B-cell malignancies as a single agent. The clinical activities of Ibrutinib as a drug were shown in the B-cell malignancies, especially in patients with CLL, mantle cell lymphoma (MCL), and Waldenstrom's macroglobulinemia (WM). Ibrutinib has generated the most extensive results so far in patients with CLL, predominately refractory or relapsed CLL where durable disease control as well as improved progression-free survival (PFS) and overall survival (OS) has been observed. The aim of this review is to outline the pharmacophysiological basis of Ibrutinib treatment as well as the current clinical experience based on the trials. The treatment algorithms of B-lymphoproliferative diseases will continue to be revised to a more personalized approach to treat with improved efficacy devoid of unnecessary toxicity.Öğe Idelalisib at the Crossroads of B-Cell Lymphoproliferative Disorders(Akad Doktorlar Yayinevi, 2016) Aksu, Salih; Ayyildiz, Orhan; Etgul, Sezgin; Goker, Hakan; Gunes, Gursel; Haznedaroglu, Ibrahim C.; Ilhan, Osman; Kaynar, Leyla G.; Malkan, Umit Y.; Ozdemir, Evren; Saydam, Güray; Sayinalp, Nilgun; Sahin, Fahri; Turgut, Mehmet; Unal, AliPhosphatidylinositol 3-kinases (PI3Ks) are considered as lipid kinases that are very active in the pathobiology of lymphoproliferative disorders (LPDs). Idelalisib, a selective inhibitor of the delta isoform of PI3K, provides significant clinical efficacy and has an acceptable side-effect profile in the treatment of B-LPDs. The aim of this review is to outline the pharmacobiological basis of idelalisib that is located at the crossroads of B-LPDs. The PI3K signaling pathway with downstream targets including Akt is involved in hematologic malignancies and lymphomas. Idelalisib has been most widely studied in chronic lymphoid leukemia (CLL) and B-lymphoma. The activity of idelalisib in high-risk FL with early relapse following front line immunochemotherapy was recently shown. The unique immunological toxicity pattern of idelalisib was also decribed in this review. Further clinical investigations will help for the better selection of the subsets of the patients with B-LPD that would be best candidates for the clinical utilization of idelalisib. Other indications such as marginal zone lymphoma, mantle cell lymphoma, Waldenstrom's Macroglobulinemia and other B-cell disorders could likely to be expanded. Future clinical and experimental data combined with the next-generation genomics strategies and personalized medicine for the treatment of malignant disorders will enlightened us for better placement of idelalisib in the treatment algorithm of the patients.Öğe Incidence and risk factors for hepatic sinusoidal obstruction syndrome after allogeneic transplantation: Retrospective multicenter study of Turkish hematology research and education group (THREG), updated data(Nature Publishing Group, 2019) Soyer, Nur; Gunduz, Mehmet; Tekgunduz, Emre; Deveci, Burak; Ozdogu, Hakan; Sahin, Handan Haydaroglu; Turak, Esra Ermis; Okay, Mufide; Kuku, Irfan; Hindilerden, Ipek Yonal; Topcuoglu, Pervin; Altuntas, Feviz; Karadogan, Ihsan; Pehlivan, Mustafa; Unal, Ali; Goker, Hakan; Erkurt, Mehmet Ali; Besisik, Sevgi Kalayoglu; Vural, FilizÖğe Long-Term Outcomes of Allogeneic Stem Cell Transplantation for Relapsed/Refractory Hodgkin and Non-Hodgkin Lymphoma: Multi-center Experience from Turkey(Springer India, 2024) Uysal, Ayse; Soyer, Nur Akad; Ozdogu, Hakan; Goker, Hakan; Cinar, Olgu Erkin; Deveci, Burak; Yilmaz, Asu FergunThis multicenter retrospective study evaluated the efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on survival and safety in patients with relapsed/refractory (R/R) Hodgkin lymphoma (HL) and non-Hodgkin lymphoma (NHL). A total of 110 patients with R/R HL or NHL who underwent allo-HSCT between July 2007 and October 2022 at 7 adult stem cell transplant centers were evaluated. Progression-free survival (PFS), graft versus host disease-free survival (GRFS), and overall survival (OS) were the primary endpoints, and NRM was the secondary endpoint. Forty-one (37.3%) of the total patients were diagnosed with HL, 69 (62.7%) with NHL. The median age at the time of allo-HCT was 39.5 years (16-67), of which 66 (60%) were male. The median follow-up was 67.5 +/- 8.1 months, and the rates of 5-year OS, PFS, and GRFS were 38.4%, 37%, and 34.8%, respectively. On multivariate analysis, CR/PR disease status after allo-HCT was significantly associated with longer PFS (HR: 13.47, 95% CI: 5.80-31.26, p = 0.000) and OS (HR: 5.23, 95% CI: 2.93-9.34, p = 0.000). CR/PR disease status after allo-HCT (HR: 5.79, 95% CI: 3.22-10.40, p = 0.000) and grade 1-2 acute GvHD (HR: 2.33, 95% CI: 1.25-4.35, p = 0.008) were significantly associated with longer GRFS. The 5-year cumulative incidence of NRM was 24.8% (95% CI, 12.5-36.7). The most common conditioning regimen was reduced intensity. Transplant outcomes are not influenced by disease subtype. However, the achievement of a CR/PR response after allo-HCT significantly prolongs OS, PFS and GRFS. In addition, the presence of acute grade 1-2 GvHD was found to be another factor prolonging GRFS. These results support the feasibility of allo-HCT, especially in heavily treated patients.Öğe Prophylactic Central Nervous System Irradiation Is Not Indispensable in Adult Patients with Acute Lymphoblastic Leukemia: A Multicenter Retrospective Cohort Study(Galenos Publ House, 2022) Cinar, Olgu Erkin; Goker, Hakan; Fidan, Kemal; Aydin, Oznur; Pashayev, Tural; Malkan, Umit Yavuz; Velet, MustafaObjective: Studies comparing the efficacy and safety of prophylactic regimens for central nervous system (CNS) involvement in acute lymphoblastic leukemia (ALL) are scarce in adults. This multicenter retrospective study aimed to compare the efficacy of prophylactic regimens with and without CNS irradiation on the development of CNS relapse during follow-up. Materials and Methods: This was a multicenter comparative cohort study. A total of 203 patients were included from four tertiary care centers in Turkey. Patients were divided into two groups according to whether they received CNS irradiation or not. The groups were analyzed retrospectively regarding patient and disease characteristics, with the main focus being CNS relapse. Results: While 105 patients received chemotherapy-based prophylaxis, 98 patients received additional CNS irradiation. These groups were statistically comparable in terms of demographic characteristics and risk factors for CNS involvement. In the irradiation group, patients were younger and had more stem cell transplants. In a median of 23.8 (11.1-62.4) months, there was no difference between the two groups regarding CNS relapse-free survival (log-rank p=0.787). Conclusion: Craniospinal irradiation may not be indispensable for every adult patient with ALL, similarly to pediatric patients. It is crucial to avoid the long-term toxicities of radiation, especially in patients with long life expectancy. Craniospinal irradiation may be reserved for therapeutic use in cases of CNS relapse and prophylaxis for some high-risk patients.
